Ethyl Acetate → HCID 86707405, compound

HRID 338838Notes

Reaction equation

HRID 338838 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]3[N:16]4[CH:17]=[C:18]([CH:21]([N:26]5[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:27]5)[C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:20][C:15]4=[N:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.P([CH:52]1[CH2:57][CH2:56]CCC1)(C1CCCCC1)C1CCCCC1.C1(B(O)O)CC1.C(OCC)(=O)C>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:56]1([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][C:8]([C:12]4[N:16]5[CH:17]=[C:18]([CH:21]([N:26]6[CH2:30][CH2:29][C@H:28]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:35])([CH3:37])[CH3:36])[CH2:27]6)[C:22]([F:25])([F:23])[F:24])[CH:19]=[CH:20][C:15]5=[N:14][N:13]=4)=[N:9]3)=[CH:4][CH:3]=2)[CH2:57][CH2:52]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 86707406HCID 86707406, compound

Product 1

HCID 86707405HCID 86707405, compoundYield 862.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A solution of tert-butyl (3S)-1-(1-(3-(7-bromo quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (Example 2, Step A; 0.25 g, 0.42 mmol), Pd(OAc)2 (0.0048 g, 0.021 mmol), P(Cy)3 (0.013 g, 0.047 mmol), and cyclopropylboronic acid (0.073 g, 0.85 mmol) in toluene (4 mL) and water (0.4 mL) was stirred at 100° C. for 6 hours. After cooling to ambient temperature, ethyl acetate (20 mL) and water (5 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (ethyl acetate) to give tert-butyl (3S)-1-(1-(3-(7-cyclopropylquinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (0.224 g, 95.9%) as a solid.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-371844b778a748c0bacd02fec737173e
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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